Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects

Cancer stem cells (CSCs) with their self-renewal ability are accepted as cells which initiate tumors. CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies, including radiotherapy and chemotherapy. Chimeric antigen receptor (CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens (TAAs) by which they accurately target and kill cancer cells. In recent years, CAR-T cell therapy has shown more efficiency in cancer treatment, particularly regarding blood cancers. The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy. Here we review the CSC markers that have been previously targeted with CAR-T cells, as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future. Furthermore, we will detail the most important obstacles against CAR-T cell therapy and suggest solutions. Cancer stem cells play key roles in tumor initiation, progression, metastasis and resistance to conventional anticancer therapies. Therefore, development of more effective therapies such as CAR-T cell therapy will transform CSC-derived tumors into a curable disease. However, this approach should be considered only after addressing some concerns such as off-tumor toxicities. [Display omitted]